Recent Advances in Biomarkers for Parkinson’s Disease

Parkinson’s disease (PD) is one of the common progressive neurodegenerative disorders with several motor and non-motor symptoms. Most of the motor symptoms may appear at a late stage where most of the dopaminergic neurons have been already damaged. In order to provide better clinical intervention and treatment at the onset of disease, it is imperative to find accurate biomarkers for early diagnosis, including prodromal diagnosis and preclinical diagnosis. At the same time, these reliable biomarkers can also be utilized to monitor the progress of the disease. In this review article, we will discuss recent advances in the development of PD biomarkers from different aspects, including clinical, biochemical, neuroimaging and genetic aspects. Although various biomarkers for PD have been developed so far, their specificity and sensitivity are not ideal when applied individually. So, the combination of multimodal biomarkers will greatly improve the diagnostic accuracy and facilitate the implementation of personalized medicine

Factors Associated With Dyskinesia in Parkinson's Disease in Mainland China

Background and Objectives: Studies examining the risk factors for dyskinesia in Parkinson's disease (PD) have been inconsistent, and racial differences exist. Since there have been no systematic studies of the characteristics of dyskinesia in the Mainland Chinese population, we sought to elucidate the risk factors for dyskinesia.Methods: A total of 1974 PD patients from Mainland China were systematically investigated by univariable and multivariable analyses. PD patients with and without dyskinesia were stratified into 4 groups according to levodopa equivalent daily dose (LEDD) and analyzed by a Cox proportional hazards model. A longitudinal study of 87 patients with dyskinesia was classified into 3 groups according to the duration from onset of PD to the initiation of levodopa, and comparisons among groups were analyzed by the Mann-Whitney test.Results: Early age of onset, long disease duration, being female, high LEDD, low UPDRS III scores (ON-state) and high Hoehn-Yahr stage (ON-state) were predictors of dyskinesia. Dyskinesia was levodopa dosage-dependent, and the incidence increased remarkably when LEDD exceeded 300 mg/d (p < 0.05). The emergence of dyskinesia had no association with the initiation time of levodopa, and if the latter was more than 4 years, the duration of time on chronic levodopa free of motor complications was significantly shortened.Conclusions: We found risk factors for the prediction of dyskinesia. Our data shows that physicians should be cautious if the LEDD exceeds 300 mg/d. The development of dyskinesia was not correlated with the time of levodopa initiation

Constructing prediction models for excessive daytime sleepiness by nomogram and machine learning: A large Chinese multicenter cohort study

ObjectiveAlthough risk factors for excessive daytime sleepiness (EDS) have been reported, there are still few cohort-based predictive models for EDS in Parkinson’s disease (PD). This 1-year longitudinal study aimed to develop a predictive model of EDS in patients with PD using a nomogram and machine learning (ML).Materials and methodsA total of 995 patients with PD without EDS were included, and clinical data during the baseline period were recorded, which included basic information as well as motor and non-motor symptoms. One year later, the presence of EDS in this population was re-evaluated. First, the baseline characteristics of patients with PD with or without EDS were analyzed. Furthermore, a Cox proportional risk regression model and XGBoost ML were used to construct a prediction model of EDS in PD.ResultsAt the 1-year follow-up, EDS occurred in 260 of 995 patients with PD (26.13%). Baseline features analysis showed that EDS correlated significantly with age, age of onset (AOO), hypertension, freezing of gait (FOG). In the Cox proportional risk regression model, we included high body mass index (BMI), late AOO, low motor score on the 39-item Parkinson’s Disease Questionnaire (PDQ-39), low orientation score on the Mini-Mental State Examination (MMSE), and absence of FOG. Kaplan–Meier survival curves showed that the survival prognosis of patients with PD in the high-risk group was significantly worse than that in the low-risk group. XGBoost demonstrated that BMI, AOO, PDQ-39 motor score, MMSE orientation score, and FOG contributed to the model to different degrees, in decreasing order of importance, and the overall accuracy of the model was 71.86% after testing.ConclusionIn this study, we showed that risk factors for EDS in patients with PD include high BMI, late AOO, a low motor score of PDQ-39, low orientation score of MMSE, and lack of FOG, and their importance decreased in turn. Our model can predict EDS in PD with relative effectivity and accuracy

The effect of esketamine combined with propofol-induced general anesthesia on cerebral blood flow velocity: a randomized clinical trial

Abstract Background Esketamine is increasingly used in clinical anesthesia. The effect of esketamine on the blood flow velocity of the middle cerebral artery has a clinical guiding effect. To investigate the effect of esketamine combined with propofol-induced general anesthesia for endotracheal intubation on the blood flow velocity of middle cerebral artery and hemodynamics during the induction period. Methods The randomized clinical trial included 80 patients aged 20-65 years who would undergo non-intracranial elective surgery under general anesthesia in our hospital from May 2022 to May 2023. The participants were divided into two groups based on anesthesia drugs: sufentanil 0.5μg/kg (group C) or 1.5mg/kg esketamine (group E). The primary outcome was variation value in average cerebral blood velocity. The secondary outcomes included cerebral blood flow velocities (CBFV), blood pressure (BP) and heart rate (HR) at four different time points: before induction of general anesthesia (T0), 1 min after the induction drug injected (T1), before endotracheal intubation (T2), and 1min after endotracheal intubation (T3). The occurrence of hypotension, hypertension, tearing and choking during induction was also documented. Results The variation of average CBFV from time T0 to T2(ΔVm1) and the variation from time T3 to T0 (ΔVm2) were not obviously different. The median consumption of intraoperative sufentanil in group C was obviously lower than that in group E. At T1, the mean HR of group E was significantly higher than that of group C. At T2 and T3, the BP and HR of group E were obviously higher than that of group C. At T2, the CBFV in the group E were obviously higher than those in the group C. The incidence of hypotension was significantly reduced in the group E compared with the group C. There were no differences in the other outcomes. Conclusions The induction of esketamine combined with propofol does not increase the blood flow velocity of middle cerebral artery. Esketamine is advantageous in maintaining hemodynamic stability during induction. Furthermore, the administration of esketamine did not result in an increased incidence of adverse effects. Trial Registration 15/06/2023 clinicaltrials.gov ChiCTR2300072518 https://www.chictr.org.cn/bin/project/edit?pid=176675